T-cells are the patient’s own cancer-killing immune system cells. Myeloma treatments such as CAR T-cell or bispecific antibody therapy help enhance the patient’s T-cells to kill cancer cells more effectively. 

T-cell exhaustion occurs when those T cells get overworked (or overstimulated) through medications or disease and stop working, which could end in disease relapse.  

At the American Society of Hematology (ASH) meeting, Dr. Nezar Mehanna from Stony Brook University in Stony Brook, NY, presented poster 3326, titled T-Cell Exhaustion Signature Predicts Early Relapse after Autologous Stem Cell Transplant for Multiple Myeloma. 

Study Details

In this poster, Dr. Mehanna presents information about their T-cell exhaustion study, in which the research team used flow cytometry-based immune phenotyping to identify T-cell biomarkers that predict early relapse following an autologous stem cell transplant in multiple myeloma patients.

There were 96 study participants comprising two groups: an early relapse group (ER), consisting of 51 individuals, defined as having relapse within 24 months from transplant, and a long-term responder group (LR), with 45 individuals, consisting of those who remain myeloma free for over four years. 

Study Methods 

Peripheral blood samples were collected from the study participants 90 days post-stem cell transplant. Those samples were analyzed using a high-dimensional FlowSOM algorithm, which clustered events based on the similarity of the expression profiles of different surface markers. This revealed 20 different cell clusters, which showed a significant amount of variables based on the patient's immune system, mainly the expression of different proteins on the surface of the T-cell. 

Each cluster was broken down based on expression into CD4 and CD8 effector and memory subsets. They first questioned whether there were differences in the abundance of different cell clusters for each group. The results showed three clusters that were more abundant than others found in multiple subsets. 

Secondly, they questioned whether there were differences in the expression of positive and negative co-signatory markers within each group. It showed 105 statistically significant results, with many markers showing differential expression in multiple cell clusters.

Conclusion 

Overall, they found that three months post-transplant, there was a distinct signature of T-cell exhaustion that was already present but only minor alterations in T-cell subset abundance. 

According to the lead investigator, Dr. Mehanna, it is early in the study, and they hope to enroll more patients to see if they can find the same results. The long-term goal of the project is to perform a blood test on a patient before they receive a transplant so they have a better idea of prognosis.

It is essential to know that autologous stem cell transplant in myeloma is very standard and greatly benefits patients. Some benefit exceptionally well, and others are not as fortunate. A lot of research is going on to predict better which patients will be which, which can help with the counseling and discussion with your physician. 

ASH 2023 Resources

Would you like to watch ASH 2023 myeloma research interviews from the investigators themselves? Click "ASH 2023" here: HealthTree University Conference Coverage

To read other ASH 2023 articles, click here: HealthTree 2023 ASH Articles